Features of mitochondrial hormone and receptor levels in aggressive endometrial cancer subtypes

Serous endometrial carcinoma (SEC) and clear cell endometrial carcinoma (CCEC) are among the most aggressive subtypes of endometrial cancer (EC), characterized by a high risk of recurrence and metastasis. Mitochondria play a key role in steroidogenesis and cellular metabolism; however, their contribution to hormonal and metabolic tumor adaptation in rare forms of EC remains poorly understood.
Purpose of the study. To comprehensively assess the levels of sex hormones, their receptors, cortisol, and glutathione in mitochondria isolated from SEC and CCEC tissues.
Patients and methods. This prospective study included 41 patients with rare forms of EC. Mitochondria were isolated from tumor tissues – 21 SEC and 20 CCEC. The control group was composed of 20 samples of endometrium unaffected by tumour. Concentrations of estrone, estradiol, estriol, testosterone, progesterone, estrogen receptors (REα, REβ), androgen receptors, progesterone receptors (RP4), cortisol, cholesterol, and glutathione were determined by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Statistica 10.0 software.
Results. In mitochondria obtained from SEC and CCEC, compared with tumor-free endometrial mitochondria, levels of testosterone and progesterone were increased by an average of 1.5‑fold, estriol by 1.8‑fold and 2.2‑fold, REβ by 3.5‑fold and 1.8‑fold, RP4 by 2.4‑fold and 5.2‑fold, and the REβ/REα ratio by 2.2‑fold and 1.9‑fold, respectively. Estradiol, REα, and androgen receptor levels exceeded control values only in SEC mitochondria, by 2.0‑fold, 1.8‑fold, and 2.2‑fold, respectively. Cortisol and cholesterol concentrations in mitochondria from rare endometrial cancer subtypes were 1.9–2.5‑fold higher than in tumor-free endometrial mitochondria, while glutathione levels were increased by 1.9–2.4‑fold.
Conclusion. SEC and CCEC are characterized by the formation of a unique mitochondrial hormonal microenvironment with estriol predominance and a high REβ/REα ratio, which may mediate suppression of apoptosis and enhanced proliferation. Differences in receptor profiles indicate distinct mechanisms of hormonal signaling, potentially determining specific features of the clinical course of each tumor subtype. Accumulation of cholesterol and cortisol in the context of elevated glutathione levels indicates metabolic reprogramming aimed at sustaining steroidogenesis and resistance to oxidative stress and apoptosis.

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